Document 0716 DOCN M9480716 TI Cytomegalovirus infection of human retinal tissue: an in vivo model. DT 9410 AU DiLoreto D Jr; Epstein LG; Lazar ES; Britt WJ; del Cerro M; Department of Neurobiology and Anatomy, University of Rochester; School of Medicine, New York. SO Lab Invest. 1994 Jul;71(1):141-8. Unique Identifier : AIDSLINE MED/94315864 AB BACKGROUND: Cytomegalovirus (CMV) retinitis is a common, devastating complication of AIDS. Strict host specificity of human CMV (HCMV), has limited the study of the virus. The purpose of this research was to create a model that allowed the in vivo infection of human retinal tissue with HCMV. EXPERIMENTAL DESIGN: Small fragments of 13-week human fetal retina were transplanted into the anterior chambers of immune-deficient mice. One week later, 15 of 30 grafts were inoculated with HCMV. Infected and noninfected specimens were compared for histopathologic changes at 14, 30, and 60 days at light and electron microscopic levels. Histochemistry was performed to characterize: level of graft differentiation, range of viral replication cycle, and effects on neuronal, glial, and monocytic elements of the retina. RESULTS: At 30 and 60 days, grafts were well differentiated histologically and histochemically. The infected grafts showed numerous large cells containing intranuclear and intracytoplasmic inclusions. Ultrastructural examination revealed viral particles within cytoplasm and nuclei. Infected cells expressed proteins representative of all phases of the HCMV replication cycle. Most HCMV-infected cells expressed the neuronal marker, protein gene product 9.5. In a second series of experiments, tissue from one graft harvested at 45 days postinfection was used to recover HCMV in fibroblast cultures and also used successfully to passage the virus to two control grafts. CONCLUSIONS: This model allows HCMV to actively infect and replicate within highly differentiated human neural tissue. It produces pathology characteristic of CMV-infected neural tissue in a time course suitable for long-term study. The nature of this model will allow the study of: the replication properties of HCMV in nervous tissue, the specific effects of HCMV on the human retina, the interaction of HCMV with other viruses, e.g., HIV, and various anti-viral therapies. DE Animal *Cytomegalovirus Infections/MICROBIOLOGY/PATHOLOGY Disease Models, Animal Fetal Tissue Transplantation Human Mice Mice, SCID Microscopy, Electron Retina/*EMBRYOLOGY/MICROBIOLOGY/PATHOLOGY *Retinal Diseases/MICROBIOLOGY/PATHOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transplantation, Heterologous Virus Replication JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).